The invention concerns an array and a method for dosing a hormone, in particular insulin, which is suitable for regulating blood glucose in a patient.
Diabetes mellitus is a metabolic disease in which the regulation of the glucose content of blood to a level appropriate for intermediary metabolic requirements is disturbed by a deficiency in insulin. Conventionally diabetes patients counteract an increase in the glucose concentration by injecting exogenous insulin. The amount to be administered is determined empirically on the basis of blood sugar self tests. It has already been proposed to improve the sugar determination by taking samples in fat tissue continuously or at intervals by means of a microdialysis probe and automatically evaluating the tissue glucose level as a measure for blood glucose.
DD 282 616 A5 describes a device for the load-adjusted control of infusion pumps whose insulin supply to the diabetic is either controlled automatically by a blood glucose sensor or semi-automatically by means of a microcomputer using patient-specific insulin dosage profiles. The input side of the microcomputer is coupled to a heart rate sensor in order to switch between so-called positive and negative insulin glucose characteristics when a threshold is exceeded. Hence during a load situation this enables a time-dependent reduction of the dosage according to an empirical function i.e. a lowering of the plasma insulin concentration, instead of the sensory control.
It is known from EP-A 0 824 240 that so-called individual-specific insulin activity equivalents can be determined with the aid of a computer from exercise heart rate data based on a physiological model of glucose/insulin metabolism which are intended to be used for learning and training programs as well as in further education.
With this as the starting point the object of the invention is to provide an array and method of the type stated above which improves the dosage of a hormone influencing blood glucose and can be optimized by taking into account the patient's condition. In particular it should enable the patient to keep his blood sugar level permanently in the normoglycaemic range by appropriate hormone doses.
The combination of features stated in the claims is proposed to achieve this object. Advantageous embodiments and further developments of the invention follow from the dependant claims.
The essence of the invention is to provide a controlling means for the fine regulation of the hormone dosage in which influences that can only be detected by the control with a time shift are at least partially compensated by anticipating coarse pre-control. Correspondingly a system having the following features is proposed according to the invention:                a measuring device for detecting measured values correlatable with blood glucose;        a controlling means which comprises a controller to process the measured values according to a control algorithm and a hormone dosing unit to administer a hormone dose;        a pilot control device (14) acting on the controlling means (12) to reduce the dead time of the control.        
The coarse pre-control can considerably improve the control performance. In particular changes in the metabolic state caused by external influences or transport processes inside the body can be taken into account in a quasi anticipating manner without a dead time so that deviations remain limited to a small range and excessive glucose values are avoided a priori. This allows an optimal dosage to be obtained for adjusting a normoglycaemic blood glucose level.
This can be advantageously achieved by the pilot control device having an anticipatory action on the controlling means in accordance with an influencing variable that is detected by sensors.
According to a particularly preferred embodiment of the invention the degree of physical activity of the diabetic is taken into consideration by the pilot control device having an activity measuring unit for the sensory detection of the degree of physical activity of the patient. With regard to the differentiated detection of resting states of the patient such as lying, sitting, standing, an advantageous embodiment provides that the pilot control device has a position sensor and in particular a mercury switch or spirit level. In order to detect states of movement it is advantageous when the pilot control device has a movement sensor in particular a pedometer. Also with regard to an indirect detection of physical strain it is advantageous when the pilot control device has a sensor for detecting body parameters of the patient such as heart rate, body temperature or skin conductivity.
A further preferred embodiment of the invention provides that the pilot control device has a basal control element for the continuous pre-administration of a preferably patient-specific basal dose of the hormone. This would cover an existing basic requirement while the controller remains at a favourable working point. A further improvement is achieved by the basal control element having a correction stage to adapt the basal dose to changes in the hormone sensitivity of the patient during the day. In order to also correct for the exogenous glucose surge it is of particular advantage when the pilot control device has a bolus control member to pre-administer hormone boli depending on the food intake of the patient. It is also advantageous for the pilot control device to have a timer for the time-dependent determination of the basal dose or to determine the time for administering the hormone boli. In order to be able to additionally take into consideration the influence of physical activity in the basal and bolus dose it is advantageous when the basal control element and/or bolus control element are connected downstream of the activity measuring device. A further advantageous embodiment provides that the pilot control device has an input unit to enter data and in particular the times of day and bread units of the patient's food intake.
The pilot control device can act on the controlling means by having a set-point output connected to the controller in order to pre-set a command variable. Other advantageous methods are to connect the pilot control device and the controller on the output side via a summation element to the hormone dosage unit or to provide the pilot control device with means for selecting the control algorithm or to pre-set control parameters of the controller.
In order to prevent operating errors it is proposed that the pilot control device has a monitoring stage that monitors and limits the hormone dose, optionally after registering critical conditions of the patient such as abnormal body temperature.
According to a further advantageous embodiment of the invention the measuring device has a glucose sensor which preferably utilizes microdialysis technology to detect tissue glucose values as measured values. This allows a continuous detection of the regulating variable without having to maintain a direct access to the blood circulation. In this case the pre-control is particularly advantageous since the glucose transfer between blood and tissue occurs with a certain delay.
Provided the hormone to be administered is insulin, the operating range of the controller should be limited to positive values. It would also be fundamentally possible to utilize a negative operating range by dosing counter-insulin hormones such as glucagon. In any case it is advantageous when the pilot control device acts on the controlling means while maintaining an adjustment reserve.
In view of the special characteristics of glucose metabolism an optimal control behaviour or control result can be achieved by designing the controller as a condition controller in which the control algorithm has a program routine acting as observer of the measured values and hormone dosage values in order to estimate non-measurable variables of state and in which the controller has a proportional-integral element to deal with disturbance variables.
It is proposed that the hormone dosage unit comprises a dosage pump designed for preferably subcutaneous hormone infusion as the actuator of the controlling means. For safety reasons the control loop can be closed by a deliberate act of the patient preferably in that the hormone dosage unit has a triggering element to manually confirm a planned hormone administration. It is also basically conceivable with regard to reducing the risks that the hormone dosage unit is only designed to display and/or provide or measure a hormone dose which is administered by the patient himself.
In order to allow the patient to have a flexible lifestyle an advantageous embodiment provides that the measuring device, the controlling means and the pilot control device are in the form of a small portable instrument that can be carried on the body of the patient.
The aforementioned object is achieved with regard to the process in that                measured values that can be correlated with blood glucose are detected;        the measured values are fed to a controlling means in which a controller processes the measured values according to a control algorithm and outputs a hormone dose to a hormone dosage unit;        the controlling means (12) for the fine dosing of the hormone is pre-controlled by a pilot control device (14) to reduce the dead time.        